API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-κB binding elements

Evidence for a positive feed-back loop pathway resulting in unremitting NF-κB activation

Yoshitaka Hosokawa, Hiroko Suzuki, Masao Nakagawa, Tae Ho Lee, Masao Seto

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-κB signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-κB binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-κB p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)- carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-κB activation.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume334
Issue number1
DOIs
Publication statusPublished - 2005 Aug 19

Fingerprint

Transcriptional Activation
Marginal Zone B-Cell Lymphoma
Fusion reactions
Genes
Chemical activation
Feedback
Tissue
Assays
Genetic Translocation
Proteins
Gene Fusion
Electrophoretic Mobility Shift Assay
Lymphoid Tissue
Luciferases
Electrophoretic mobility
Mucous Membrane
Experiments

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-κB binding elements: Evidence for a positive feed-back loop pathway resulting in unremitting NF-κB activation",
abstract = "t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-κB signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-κB binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-κB p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)- carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-κB activation.",
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T2 - Evidence for a positive feed-back loop pathway resulting in unremitting NF-κB activation

AU - Hosokawa, Yoshitaka

AU - Suzuki, Hiroko

AU - Nakagawa, Masao

AU - Lee, Tae Ho

AU - Seto, Masao

PY - 2005/8/19

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N2 - t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-κB signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-κB binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-κB p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)- carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-κB activation.

AB - t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-κB signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-κB binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-κB p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)- carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-κB activation.

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